Factors influencing the effects of murine cytomegalovirus on the pancreas

Background As human cytomegalovirus(HCMV) infections are implicated in insulin-dependent diabetes mellitus (IDDM), the effects of murine (M)CMV infection of inbred mice on the pancreas are of interest.Results Inflammation and periacinar oedema peaked on day 3 and were replaced by a focal inflammation, but infected cells were rare. The islets were spared in C57BL mice. Insulitis normally seen in non-obese diabetic (NOD) mice was accelerated, but infected NOD mice did nor become glycosuric. Isotypes of total and autoreactive antibodies suggested a shift to a Th1 response (IgG(2a)) in all MCMV-infected mice. MCMV-induced pancreatitis was not affected by MHC genes but was similar or less severe in BALB/c mice. As these lack the Cmv1 gene, which provides a protective natural killer (NK) cell response in C57BL congenic mice, the C57BL background may carry a pancreatitis susceptibility gene able to counter NK-mediated restriction of viral replication. Consistently, congenic mice expressing Cmol on a BALB/c background did not display pancreatitis, unless depleted of NK cells. In vivo treatment with soluble cytokine receptors suggested that interleukin 1 (IL-I) and/or tumour necrosis factor alpha contribute to acinar necrosis in C57BL mice.